title: New dicoumarol sodium compound: crystal structure, theoretical study and tumoricidal activity against osteoblast cancer cells.
abstract: BACKGROUND
  Enormous interest had been paid to the coordination chemistry of alkali and alkaline metal ions because of their role inside body viz; their Li(+)/Na(+) exchange inside the cell lead to different diseases like neuropathy, hypertension, microalbuminuria, cardiac and vascular hypertrophy, obesity, and insulin resistance. It has been presumed that alkali metal ions (whether Na(+) or K(+)) coordinated to chelating ligands can cross the hydrophobic cell membrane easily and can function effectively for depolarizing the ion difference. This unique function was utilized for bacterial cell death in which K(+) has been found coordinated valinomycin (antibiotic).
  
  
  RESULTS
  Distinct sodium adduct (1) with dicoumarol ligand, 4-Hydroxy-3-[(4-hydroxy-2-oxo-4a,8a-dihydro-2H-chromen-3-yl)-phenyl-methyl]-chromen-2-one (L) is isolated from the saturated solution of sodium methoxide. Single crystal X-ray diffraction studies of the adduct reveals that sodium is in the form of cation attached to a methoxide, methanol and a dicoumarol ligand where carbonyl functional groups of the coumarin derivative are acting as bridges. The sodium compound (1) is also characterized by IR, (1)H-NMR, and (13)C{(1)H}-NMR spectroscopic techniques. The composition is confirmed by elemental analysis. DFT study for 1 has been carried out using B3LYP/6-13G calculations which shown the theoretical confirmation of the various bond lengths and bond angles. Both the compounds were studied subsequently for the U2OS tumoricidal activity and it was found that L has LD50 value of 200 μM whereas the sodium analog cytotoxicity did not drop down below 60%.
  
  
  CONCLUSIONS
  A sodium analogue (1) with medicinally important dicoumarol ligand (L) has been reported. The crystal structure and DFT study confirm the formation of cationic sodium compound with dicoumarol. The ligand was found more active than the sodium analog attributed to the instability of 1 in solution state. Coumarin compound with sodium was observed to be less cytotoxic than the ligand, its LD50 value never dropped below 60%.
authors.affiliation: Institute of Chemical Sciences, University of Peshawar, Peshawar, Pakistan ; Department of Chemistry, Sarhad University of Science and Information Technology, Peshawar, Pakistan.
authors.forename: Sadia
authors.initials: S
authors.lastname: Rehman
authors.affiliation: Department of Chemistry, Sarhad University of Science and Information Technology, Peshawar, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ikram
authors.affiliation: Institute of General, Inorganic and Theoretical Chemistry, University of Innsbruck Innrain 80-82, A-6020 Innsbruck, Austria.
authors.forename: Ajmal
authors.initials: A
authors.lastname: Khan
authors.affiliation: Trinity Biomedical Sciences Institute (TBSI) School of Biochemistry and Immunology Trinity College, Dublin 2, Ireland.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Min
authors.affiliation: Trinity Biomedical Sciences Institute (TBSI) School of Biochemistry and Immunology Trinity College, Dublin 2, Ireland.
authors.forename: Effat
authors.initials: E
authors.lastname: Azad
authors.affiliation: Institute of General, Inorganic and Theoretical Chemistry, University of Innsbruck Innrain 80-82, A-6020 Innsbruck, Austria.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Hofer
authors.affiliation: Trinity Biomedical Sciences Institute (TBSI) School of Biochemistry and Immunology Trinity College, Dublin 2, Ireland.
authors.forename: Kh
authors.initials: Kh
authors.lastname: Mok
authors.affiliation: School of Chemistry, University of Dublin Trinity College, Dublin 2, Ireland.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Baker
authors.affiliation: School of Chemistry, The University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Blake
authors.affiliation: Institute of Chemical Sciences, University of Peshawar, Peshawar, Pakistan.
authors.forename: Saeed Ur
authors.initials: SU
authors.lastname: Rehman
keywords: Bone cancer; DFT; Dicoumarol; Single crystal study; Sodium cation